Prostate cancer is the most common malignancy in men and the second leading cause of death from cancer in the United States. Metastases are the major cause of death from cancer. Therefore, aggressive (AG) prostate cancer leads to a higher metastasis rate and requires early detection and treatment. Since the discovery of prostate-specific antigen (PSA), assays that detect this serum biomarker (together with digital rectal exams) have been used for the screening of prostate cancer. PSA testing has resulted in early detection and intervention. However, the major limitation of PSA is the low specificity and high prevalence of detecting benign prostatic hyperplasia, especially in older men. Early detection based on PSA testing also fails to distinguish aggressive prostate cancer from non-aggressive prostate cancer. Indeed, with the illustration of the limitations of the current PSA-based screening method, a recently published study randomly assigned 76 693 men at 10 U.S. study centers to receive either annual PSA screening (38 343 subjects) or usual care as the control (38 350 subjects); this study reported no statistical differences in prostate cancer specific mortality between the groups after 7-10 years of follow-up.
Besides preoperative PSA, clinical risk assessment tools for prostate cancer metastasis before surgery largely rely on the prostate biopsy Gleason score. However, the risk assessment based on this clinical criterion is too imprecise to be useful due to biopsy sampling error and interobserver grading differences. It is also unable to be used as a screening test for early detection of aggressive prostate cancer. Currently, aggressive prostate cancer is under-detected and under treated while nonaggressive prostate cancer is overdetected and overtreated. Consequences of the difficulty of distinguishing the aggressive and nonaggressive prostate cancer are that prostate cancer patients suffer from unnecessary surgeries, and health care faces massive unnecessary expenditures. Therefore, reliable biomarkers to distinguish aggressive and nonaggressive prostate cancer are badly needed to prevent patients with nonaggressive prostate cancer from overtreatment and to allow patients with aggressive cancer to receive appropriate treatment earlier in the course of their disease.